The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear and has threatened global health security. Although phenomenal efforts are in progress to effectively combat this COVID-19 outbreak. Still, no licensed antiviral drugs or vaccines are available, and treatment is limited to supportive care and few repurposed drugs. In this urgency situation, computational drug discovery methods provide both an alternative and a supplement to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has shown the most successful strategy in antiviral drug discovery. The present study deals with the identification of potential compounds that specifically interact with SARS-CoV-2 vital proteins, including main protease (Mpro), Nsp12 RNA-dependent-RNA-polymerase (RdRp) and Nsp13 helicase. A constructive and integrated virtual screening efforts together with molecular dynamics simulations identified potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, structurally important binding site residues in conserved motifs located inside the active site are elucidated, which displayed relative importance in ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study paved the way to identify and design specific targeted inhibitors to combat COVID-19 outbreak.

In the aftermath of the COVID pandemic, post-COVID-19 syndrome (PCS) remains a challenge and may continue to represent a major health problem in the future. Moreover, the influence of type 2 diabetes and being overweight on PCS remains unclear. This study aimed to assess this influence. We performed an observational study from October 2020 to July 2022, which included 466 patients (269 males and 197 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms after 1 month of COVID-19 infection. The patients were divided into four groups according to the study objectives: patients with type 2 diabetes, overweight patients, overweight patients with type 2 diabetes, and normal-weight patients without type 2 diabetes. The clinical and demographic data collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. Our results showed that type 2 diabetes patients had a more difficult course of treatment and longer hospitalization. Moreover, more type 2 diabetes patients underwent rehabilitation than the other study groups. The prevailing symptoms in our patients with PCS were dyspnea and fatigue, mostly in female patients with type 2 diabetes. Our study also showed that more women with type 2 diabetes and more overweight women with type 2 diabetes suffered from secondary infections. Further, more overweight patients were treated in the intensive care unit compared to the other groups. However, our study showed an interesting result that patients with type 2 diabetes had the shortest PCS durations. Type 2 diabetes and being overweight are risk factors for PCS onset and prolonged duration. Therefore, our data that revealed a shorter duration of PCS in type 2 diabetes patients compared to the other investigated groups was unexpected. We believe that answering this question regarding the results will enable us to improve PCS treatment in general.

The aim of this study was to estimate the association between fear of COVID-19 and risk perception with preventive behavior in health professionals from three Latin American countries. An analytical cross-sectional study was conducted. Health professionals with on-site care in Colombia, Ecuador, Guatemala, and Peru were surveyed. Information was collected through an online self-report questionnaire. The main variables were preventive behavior as the dependent variable and fear of COVID-19 and risk perception as independent variables. Linear regression was used, and Beta coefficients and p-values were calculated. 435 health professionals were included, the majority were aged 42 years or older (45.29%, 95%CI: 40.65%-50.01%) and female (67.82%, 95%CI: 63.27%-72.05%). It was shown that the greater the fear of COVID-19, the greater the preventive behavior of COVID-19 infection (B=2.21, p=0.002 for total behavior; B=1.12, p=0.037 for additional protection at work; B=1.11, p<0.010 for hand washing). The risk perception of COVID-19 infection had a slight direct relationship with preventive behaviors (B=0.28, p=0.021 for total behavior; B=0.13, p=0.015 for hand washing), with the exception of the preventive behavior of using additional protection at work (p=0.339). We found that fear and risk perception are associated with increased practice of hand washing and use of additional protection at work. Further studies are required on the influence of working conditions, job performance and the occurrence of mental health problems in frontline personnel with regard to COVID-19.

Background: The uptake of COVID-19 booster vaccines has been significantly low. Therefore, it is questionable whether combining the COVID-19 booster vaccines with Influenza vaccines can increase the population's interest in taking such vaccines and manage the health pandemic effectively. Methodology: In this systematic review and meta-analysis, a synthesis of the findings and summary of a total of 30 research articles based on the topic, ‘combining influenza and COVID-19 booster vaccination strategy’ was undertaken. The research articles were identified from three databases, namely, PubMed, Cochran Library, and Google Scholar using specific keywords and inclusion criteria. However, research articles that were not peer-reviewed and not published in English were excluded from the systematic review and meta-analysis. The average risk ratio of the included articles was 0.78% based on a 95% CI. On the other hand, the heterogeneity between such studies was I² = 35%, while the statistical significance of their findings occurred at p < 0.05. The average p-value of the included research studies was p = 0.62, implying that the null hypothesis was not rejected in almost all the studies. Results: A synthesis of the chosen research articles revealed that when influenza and COVID-19 booster vaccines are combined, there is potential for an increase in the uptake of the latter, mainly because many populations have already been accustomed to taking influenza vaccines on an annual basis. Conclusions: In this way, through such findings, medical health experts can make informed decisions to increase the population's willingness to receive the COVID-19 booster vaccines.

Given the concerns of waning immunity from the primary COVID-19 vaccines and the first booster dose, we conducted an on-line cross-sectional study in May 2022 to investigate willingness to receive a second COVID-19 booster dose or a new COVID-19 vaccine and its associated factors. Overall, 22.7% of participants were willing to be vaccinated, 39.3% were unsure, but tend to be willing, 25.8% were unsure, 4.9% were unsure, but tend to be unwilling, and 7.4% were unwilling to be vaccinated. The main reasons against accepting a second COVID‐19 booster dose or a new COVID-19 vaccine COVID-19 dose included concerns about the side effects, the opinion that further vaccination is unnecessary, and effectiveness uncertainties. Males, younger individuals, participants without a previous COVID-19 diagnosis, and those with good/very good self-perceived physical health were significantly more frequently willing to receive a second COVID‐19 booster dose or a new COVID-19 vaccine. Also, increased fear of the COVID-19, increased trust in COVID-19 vaccination and decreased fear of a second booster dose or a new COVID-19 vaccine were associated with increased willingness. Our results show some hesitancy and unwillingness toward further COVID-19 vaccination and indicate that fear of COVID-19 and trust in COVID-19 vaccination affect public opinion

The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p &lt; 0.045), Work with COVID patients - Traumatic stress (p &lt; 0.001) and Total number of COVID patients per day – Traumatic stress (p &lt; 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.

This tutorial is organized into three major sections—viruses, vaccines and the race for a Covid-19 vaccine. The goal is to provide enough background on viruses, history of vaccines, and the science of vaccinology founded on the principles of immunity. The hope is that this will enable us to understand the challenges, methods and prospects for developing a safe and effective vaccine against SARS-CoV-2. Many important viruses such as smallpox, HIV, HCV and SARS-CoV-2 which is responsible for causing the Coronavirus disease 2019 (Covid-19) are presented in detail, which is then followed by a description of different vaccine development methods and strategies. The tutorial then discusses different candidate SARS-CoV-2 vaccines and provides specific details of many of the prospective vaccines on the leader-board which are undergoing clinical trials. The tutorial concludes with a realistic projection for a safe and effective vaccine against SARS-CoV-2 based on the historical scientific record.

Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7^th edition published March 3^rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in &lt;5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in &gt;55% of vaccinees in Phase 1 and &gt;70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (&gt;73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p &lt;0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Vaccines against SARS-CoV-2 have been pivotal in overcoming the Covid-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g. people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibody-mediated angiotensin converting enzyme 2 (ACE2) binding blockade, against the SARS-CoV-2 spike (S) proteins after 1 and 2 doses of the ChAdOx1 nCoV-19 vaccine in a population of Black PLWH. Here, we report that PLWH (N = 103) did not produce an anti-S IgA response after infection or vaccination, however, anti-S IgG was detected in response to vaccination and infection, with the highest level detected for infected vaccinated participants. The anti-IgG and ACE2 blockade assays revealed that both vaccination and infection resulted in IgG production, however, only vaccination resulted in a moderate increase in ACE2 binding blockade to the ancestral S protein. Vaccination with a previous infection results in the greatest anti-S IgG and ACE2 blockade for the ancestral S protein. In conclusion, PLWH produce an anti-S IgG response to the ChAdOx1 nCoV-19 vaccine and/or infection, and ChAdOx1 nCoV-19 vaccination with a previous infection produced more neutralizing antibodies than vaccination alone.

The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring SARS-CoV-2 prevalence in a city in Northern Italy from October 2021 to May 2023. Starting from a widely applied deterministic model, this study proposed a variation to take into account population characteristics and virus biodegradation in the sewer network. The model calculated virus loads and corresponding COVID-19 cases over time in different areas of the city and was validated with healthcare data while considering viral mutations, vaccinations, and testing variability. The correlation between the predicted and reported cases was high across the three waves that occurred in the considered period, demonstrating the model’s capacity to predict relevant fluctuations in the number of cases. Population characteristics did not substantially influence the predicted and reported infection rates. Conversely, biodegradation significantly reduced the virus load reaching the wastewater treatment plant, resulting in a 30% reduction in the total virus load produced in the study area. This approach can be applied for comparing virus load values across cities with varying population demographics and sewer network structures, enhancing the comparability of WBE data for effective surveillance and intervention strategies.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

The all-pervasiveness and dynamic nature of the COVID-19 pandemic warrants comprehensive and constant surveillance of the numerous mutations that are accumulating in global SARS-CoV-2 genomes and contributing to the microevoution of the various lineages of the novel coronavirus. This would help us gain insights into the evolving pathogenicity of the virus, and thereby improvise our control and therapeutic strategies. This study explores the genome-wide frequency, gene-wise distribution, and molecular nature, of the large repertoire of point mutations detected across the global dataset of 3,608 SARS-CoV-2 RNA-genomes short-listed from a total 5,485 whole genome sequences deposited in GenBank till 4 June 2020 using a download filter that eliminated all incomplete/gapped sequences. Phylogenomic analysis involving all existing SARS-CoV-2 lineages, represented by 3,740 whole genome sequences from human-source (out of a total of 63,894 sequences stored in the GISAID repository, as on 15 July, 2020), illustrated that the two major-lineages of the virus contributed almost equivalently to the pandemic. However, entities belonging to the early lineages are still mostly spread over Asian countries, whereas those affiliated to recently-derived lineages have a relatively more global distribution. Mutation frequency in the SARS-CoV-2 pan genome was found to be 2.27 × 10^-5 nucleotide positions mutated per nucleotide analyzed. An overwhelming majority (count: 1797) of the total 2452 instances of single nucleotide substitution detected (in the SARS-CoV-2 pan genome) were found to be transition mutations with cytidine to uridine (CàU) as the most ubiquitous molecular-type (count: 987). Of the 655 instances of transversion detected, the guanosine to uridine (GàU) variant was most widespread (count: 367). All transcribed and untranscribed loci of the pan genome were found to contain mutation(s). nsp3, and S, N and orf3a, were the most point-mutation-ridden non-structural and structural protein-coding genes, respectively, with 435, 300, 171 and 128 total mutations; 349/86, 192/108, 107/64 and 76/52 transitions/transversions; and 189/48, 106/55, 59/42 and 43/31 CàU/GàU substitutions respectively. Potential mechanistic backgrounds were envisaged for the molecular bias of mutations observed in SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia, especially among older individuals and those with underlying health conditions. The C57BL/6 mouse is widely used to develop mouse models of obesity, diabetes, hypertension, and immune disorders, conditions that are associated with increased risk of severe COVID-19. Although many studies using these mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated SARS-CoV-2 expressing the fluorescent protein Venus to facilitate in vivo pathological studies using C57BL/6 mouse models. We generated a mouse-adapted strain of SARS-CoV-2, by performing sequential lung-to-lung passages in BALB/c mice, followed by in C57BL/6 mice. We observed that the C57BL/6-adapted SARS-CoV-2 (named MASCV2-p25) replicated efficiently in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6J mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent gene Venus into MASCV2-p25, and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia similar to that induced by MASCV2-p25. In addition, two-photon excitation microscopy of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two photon in vivo imaging studies of the pathogenesis of severe COVID-19 and for the development of therapeutic agents for severe pneumonia.

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC₅₀ value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in Wuhan, Hubei province, China being its epicenter in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11, 2020). COVID-19 has presently spread to more than 195 countries/territories while killing nearly 19,600 humans out of cumulative confirmed cases accounting to more than 430,000 within a short period of just a few weeks. The majority of deaths have been reported in Italy and China. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter COVID-19. The present review presents an overview of COVID-19 and the causative virus SARS-CoV-2, with particular emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread., highlighting in very brief the preventive and control measures along with a few of the recent research developments to counter this pandemic virus/disease.

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

We previously proposed a public intervention framework concept that would allow people to resume personal and economic activities. We showed that intervention measures are used in a quantitative scale to reduce transmission probabilities and disease severity. In this article, we systematically examine the origin, assumptions, performance and limitations of epidemiological models from different views used in past review. We found that nearly all model assumptions fail to hold or are remote from reality; R0 does not exit or has no utility in guiding treatment options; personalized intervention measures are vitally important to COVID-19 due to its transmission characteristic; and current epidemiological models are unable to accurately assess the true benefits of personalized intervention measures. We suggest that poor performance of the models are attributed to flawed assumption that health/disease properties can be treated as transferable properties. The flaw creates a fiction that disease properties such as infection probabilities and death risks can be transferred from any vulnerable persons to anyone in the population and thus severely limit societal ability to fight the pandemic. We finally show that the benefits of personalized mitigation measures could be determined directly by using variable Ri values for infected persons (or nodes) together assessment of death rate and disability rate; the attempt of avoiding the disease by defeating all potential transmission probabilities is unrealistic; but mitigating disease severity for specific persons is more feasible and reliable. A most reliable strategy for reviving economy is using personalized protective measures and improving person health before effective vaccine is available.

COVID-19 represents an unprecedented threat to global public health and economies. Assays are urgently needed for rapid detection and diagnosis of SARS-CoV-2-infected patients in order to inform treatment and quarantine strategies. Establishing globally accepted easy-to-access diagnostic tests is extremely important to understanding the epidemiology of the present pandemic. While nucleic acid-based tests are considered to be more sensitive with respect to serological tests, but the present gold standard RT-PCR-based assays possess limitations such as low sample throughput, requirement for sophisticated reagents and instrumentation. To overcome these shortcomings, recent efforts of incorporating LAMP-based isothermal detection, and minimizing the number of reagents required are on rise. Novel CRISPR- and other nuclease-based techniques, when merge with isothermal and allied technologies, promises to provide sensitive and rapid detection of SARS-CoV-2 nucleic acids. Here we discuss and present compilation of state-of-the-art CRISPR based detection techniques for use in COVID diagnosis and epidemiology.

In March 2020, several mass gathering events were related to the Falles festival in Borriana (Spain), resulting in a 536 laboratory-confirmed COVID-19 cases outbreak among participants. Our objective was to estimate anti-SARS-CoV-2 antibodies persistence six months after and factors associated with antibody response. A prospective population-based cohort study was carried out by the Public Health Center of Castellon and the Emergency and Clinical Analysis and Microbiology Services of Hospital de la Plana in Vila-real. In October 2020, sero-epidemiologic study to estimate the persistence of anti-SARS-CoV-2 antibodies by a electrochemiluminescence immunoassay (ECLIA) was implemented. We enrolled 484 (90.2%) of the 536 members of the initial outbreak cohort and detected persistent antibodies in 479 (99%) without re-infection episodes. Five participants had a negative antibody test. Factors associated with a negative result were a lower body mass index (BMI), and less contact with other COVID-19 cases. Among the 469 participants with two ECLIA tests, 96 (20.5%) had an increase of antibodies and 373 (79.5%) a decline. Increased antibodies were associated with older age, higher BMI, more severe illness, and low current smokers. After a COVID-19 infection, a high proportion of cases maintained detectable anti-SARS-CoV-2 antibodies.

Background. The characterization of new biomarkers of COVID-19 is extremely important. Few studies measured the soluble receptor for advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium and magnesium in COVID-19. Aims: To measure sRAGE, ACE2, interleukin (IL)-6, IL-10, CRP, calcium, magnesium, and albumin in COVID-19 patients in association with peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) including ground glass opacities. Methods. This study measured sRAGE, ACE2, IL-6, IL-10, CRP using ELISA techniques, and calcium, magnesium, and albumin using a spectrophotometric method in 60 COVID-19 patients and 30 healthy controls.Results. COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered levels of SpO2, albumin, magnesium and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients with calcium being the most important predictor followed by IL-6, and CRP. COVID-19 patients with CCTAs showed lower SpO₂ and albumin levels than those without CCTAs. SpO2 was significantly and inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium and calcium. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.Conclusion. The results show that immune-inflammatory and RAGE pathway biomarkers may be used as external validating criterion for the diagnosis COVID-19. Those pathways coupled with lowered SpO2, calcium and magnesium are drug targets that may help to reduce the consequences of COVID-19.

Conservation history of D614 residue is valuable in predicting the consequences of D614G mutation in the SARS-CoV-2 spike glycoprotein (SGP). We report here that the D614 belonged to an extraordinarily conserved, densely hydrophobic eleven amino acid peptide-motif vavlyqdvnct (11-aa), in the Sarbecovirus group and the variant carrying vavlyqdvnct had appeared in Chinese samples and became predominant in several geographical hotspots in late March, 2020. Interestingly a 2009 annotation of SARS-CoV contained the same mutation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected around 1.5 million individuals with a mortality rate ranging from 5 to 10%. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (M^Pro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of M^Pro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae M^Pro in five clusters specific to viral hosts. This clustering was also corroborated with the comparison of M^Pro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 M^Pro. In agreement with this, we performed screening of the custom-made library of ~7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 M^Pro as the primary target. We identified several natural molecules that strongly binds to SARS-CoV-2 M^Pro among which top seven molecules are d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin and Phyllaemblicin B. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp and hACE-2. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.

Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

The availability of simple SARS-CoV-2 detection methods is crucial to contain the COVID-19 pandemic. This study examined whether a commercial LAMP assay can reliably detect SARS-CoV-2 genomes directly in respiratory samples without having to extract nucleic acids (NA) beforehand. Nasopharyngeal swabs (NPS, n = 220) were tested by real-time reverse transcription (RT)-PCR and with the LAMP assay. For RT-PCR, NA were investigated. For LAMP, NA from 26 NPS in viral transport medium (VTM) were tested. The other 194 NPS were analyzed directly without prior NA extraction [140 samples in VTM; 54 dry swab samples stirred in phosphate buffered saline]. Ten NPS were tested directly by LAMP using a sous-vide cooking unit. The isothermal assay demonstrated excellent specificity (100%) but moderate sensitivity (68.8%), with a positive predictive value of 1 and a negative predictive value of 0.65 for direct testing of NPS in VTM. The use of dry swabs, even without NA extraction, improved the analytical sensitivity; up to 6% of samples showed signs of inhibition. The LAMP could be performed successfully with a sous-vide cooking unit. This technique is very fast, requires little laboratory resources and can replace rapid antigen tests or verify reactive rapid tests on site.

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. 1,150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign.

This paper surveys estimates of the transmission features of the novel coronavirus, and then proposes a model to address sample-selection bias in estimated determinants of infection. Containment assumptions of the infection forecasting models depend on assumed effects of policies and self-regulating behavior. In the commons dilemma of the pandemic, the perceived ‘low risks’ of unregulated marginal choices do not reflect the full social cost, implying non-pharmaceutical interventions (NPI) to reduce mortality can enhance social welfare. As more economic activity renews with liftings of restrictive NPI (RNPI), a critical question concerns the ability of milder NPI (MNPI) and voluntary precautions to mitigate the risk of greater infections and deaths while also limiting the pandemic’s economic damage and its social costs. Ineffective NPI could lead to continued COVID-19 waves and new types of crises, worsened expectations and delayed economic recoveries. From the central range of surveyed estimates of transmission and alternative herd-immunity-threshold estimates, a ‘worst-case’ virus guidepost suggests eventual deaths of around 25 to 41 million worldwide and 1.1 to 1.7 million in the U.S. needed to reach herd immunity with no vaccine or treatment. The most optimistic study surveyed (theoretical model from a non-reviewed preprint study) combined with the low end of the range of the estimated mortality rate suggests 6 to 9 million deaths worldwide and 250 to 370 thousand in the U.S. to reach herd immunity. Successes in the mix of NPI, treatments, and vaccine can limit the eventual global death toll of the virus. Improved estimation models for forecasting and decision making may assist in better targeting the local timings and mix of NPI. Diagnostic tests for the virus have been largely limited to symptomatic cases, causing possible sample selection bias. A recursive bivariate probit model of infection and testing is proposed along with several possible applications from cross-section or panel-data estimation. Multiple potential explanatory variables, data sources, and estimation needs are specified and discussed.

The COVID-19 pandemic had profound negative effects on millions of couples affected by infertility and in need to resort to assisted reproductive technologies. There is no consensus over the optimal way and moment of screening triage-negative asymptomatic patients and staff. We present SARS-CoV-2 antibodies’ (IgM, IgG) seroprevalence in 516 triage-negative patients and 30 fertility care providers. The sampling for SARS-CoV-2 serological assays took place from the lockdown release throughout the second half of 2020 (17.05 - 01.12.2020). It revealed an increased seroprevalence of antibodies that closely followed the local epidemiology of COVID-19, with the highest rate of seropositivity coincident with the peak of the second wave. From 546 triage-negative individuals whose blood samples were assessed for SARS-CoV-2 antibodies, 6% yielded positive results. The overall seroconversion rate was 2.8% for IgG and 5.1% for IgM. In the group with positive IgM, we observed a negative predictive value for IgM of 98.36% (95% CI: 88.79 – 99.78%), which is clinically meaningful. Serological testing of triage-negative patients up to seven days prior to the actual fertility procedure might avoid the more expensive and not more sensitive molecular testing currently being used for patient screening in most fertility units.

The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes, however more research is needed to strengthen the existing evidence basis as one of the most important limitation is the limited number of trials and the evaluation of varied therapies. The analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.

Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.

Coronaviruse disease (COVID-19) outbreak has created an emergency globally, and social distancing and isolation is the only solution to prevent its spread. Several countries have announced fully locked on to tackle this pandemic. The recent COVID-2019 has shaken the globe with incidence cases of more than half-million cases, and a mortality toll of more than twenty thousand to date. The coronavirus family is inclusive of pathogen of both – animal species and humans, encapsulating the isolated severe acute respiratory syndrome coronavirus (SARS-CoV). Researchers round the globe have been dexterously working to decode this lethal virus. Many mathematical frameworks have also been depicted which have helped to understand the dynamics of the COVID-19. Research on coronaviruses continues to explore various aspects of viral replication and pathogenesis to understanding the predilection of these viruses to switch between species, to develop an infection in a new host, and to identify significant reservoirs of coronaviruses will dramatically aid in our potential to prophesize when and where potential epidemics may occur. Many of the non-structural and accessory proteins encoded by the viruses remain unclear and unknown. This systematic review highlights the current situation of the pandemic, virus genomic composition, pathogenesis, symptomatology, diagnosis, and prognosis along with mathematical models of disease transmission and dynamics.

The increasing number of people living with Long COVID requires the development of more personalized care, as for now limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratifying people with Long COVID. Individual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified 3 patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean=2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and a poor sleep and respiratory quality of life. Cluster-Severe was characterized by a higher proportion of women and smokers as in the other clusters, with a higher number of Long COVID symptoms, in particular of vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified in 3 sub-categories in terms of severity. If replicated in other populations, this simple classification will help clinicians to personalize the care of people with Long COVID.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p &lt;0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p &lt;0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p &lt;0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

Background: COVID-19 is currently one of the most important medical challenges as it affects the entire population with children being infected as easily as adults. Objective: The study evaluated the mortality of under 17-year-olds and compare the frequency with that of adults in a cohort of 8986 COVID-19 positive patients hospitalized in a single care center. Design: retrospective clinical trial, all hospitalizations of COVID-19 positive patients as diagnosed by RT-qPCR were analyzed by revisiting their medical records. Setting: 8986 COVID-19 positive patients hospitalized in a Hospital de Base and the Infant and Maternal Hospital of São Jose do Rio Preto, SP, Brazil (HB/HCM) being these totals of 383 COVID-19 positive under 17-patients. Patients: patients COVID-19 positive under 17-year-olds were grouped by age and evaluated by analyzing their medical records. They were categorized as Group I, children, and adolescents under 19 years old and Group II, adults over 19 years. Results: Overall mortality in under 19-year-olds was 12 deaths, that is, 3.13% of the patients in this age group and 0.55% of the overall mortality from COVID-19. Mortality in the group of adults was 2197 equivalent to 24.45% of the hospitalized adults and 99.45% of overall deaths. Mortality was significantly higher for adults than for under 19-year olds (p-value < 0.0001). Regarding the different ages of children and adolescents, the number of deaths of under 1-year olds was 2/123 (1.62%), of 1-4 years it was 4/95 (2.11%), of 5-9 years it was 1/47 (2.13%), of 10-14 years it was 1/40 (2.5%) and of 15-19 years it was 4/78 (5.13%). There were no statistical differences between the different age groups ( p-value = 0.3). Conclusion: Mortality from COVID-19 in children and adolescents was lower than in adults and generally associated with other comorbidities with the main association being with heart disease.

Socio-demographic factors are responsible of health inequalities also in vaccination. The aim of this study was to evaluate their role at population level through a population-based study performed on the whole population entitled to receive COVID-19 vaccines in Umbria Region, Italy, and registered to the Regional Healthcare Service as of February 28th, 2021. Socio-demographic characteristics and vaccination status in terms of uptake at least one dose of any available vaccine, completion of the primary vaccination cycle and uptake of the booster doses as of February 28th, 2022 were col-lected from the Umbria regional database. The percentage of eligible population who did not initiate the COVID-19 vaccination, complete the full vaccination cycle and get the booster dose was 11.8%, 1.2% and 21.5% respectively. A younger age, being a not-Italian citizen, and not holding an ex-emption for chronic disease/disability and a GP/FP were associated to all the endpoints. Females, as compared to males, were more likely to not initiate the vaccination but less likely to not receive the booster dose. On the contrary, results on the deprivation index were not conclusive. The findings, beyond confirming current knowledge at population level, provide new inputs for better tailoring vaccination campaigns.

In this study, we use descriptive statistics and data visualization techniques to analyze datasets and identify patterns and relationships between bikeshare and other transportation modes. We also use regression analysis to quantify the impact of various factors on bikeshare usage. Our results indicate that bikeshare trips during the pandemic were much longer compared to pre-pandemic times. Moreover, usage of bikeshare differed by user group, with casual users showing a greater increase in usage compared to subscribers. We plotted bivariate choropleth maps to visualize the spatial distribution of changes in bikeshare usage. Our findings suggest that an increase in bikeshare travel was associated with a reduction in travel by ride-hailing and public transit, especially in the northern part of the city, indicating a potential replacement of other modes of transportation. On the western and southern boundary of the city, bikeshare had a complementary effect with other modes. Overall, the data acquired for this study provides a valuable opportunity to understand the behavior of bikeshare users in Chicago, the intercorrelation of bikeshare with other transportation modes, and the impact of infrastructure on bikeshare usage. The findings of this study can inform the design and implementation of bikeshare systems in other cities and contribute to the development of a more sustainable transportation system.

Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical challenges facing the global health system today. The possibility to identify the group of persons in the cohort of people under 50 years old, who are sensitive to the COVID-disease by non-invasive methods, is a very perspective approach for estimating the epidemiological state of the human population. The study aimed to identify the features of people's faces with COVID-19 that the most correlate with disease severity could serve as one of these approaches. For this aim, 525 photos of patients' faces with different outcomes of COVID-19 disease were analyzed using the Dlib face recognition convolutional neural network pre-trained for face recognition. Face descriptor vectors were obtained using the convolutional neural network. Facial features were found that predict a person's sensitivity to the SARS-CoV-2 virus (disease severity), and the contribution of each of the features to the risk of developing a severe form of COVID in a person was found. The accuracy of the binary classification of the individual severity of the COVID-19 course using the k-nearest neighbors algorithm on the test dataset was accuracy - 84%, AUC - 0.90.

The most severe threat that the Covid-19 pandemic poses to the global economy is the need to choose between human lives and livelihoods. Bangladesh must assess the implications of such impacts on Bangladesh's macro-financial scenario to maintain the economy's current high growth trajectory. The paper outlines the major Covid-19 shock wave transmission channels to the four major sectors of the Bangladesh economy. Authorities around the world have taken every precaution possible to halt the spread of the pandemic. An aggregate transmission framework that includes these four sectors is required to contain the impact of Covid-19 can propagate through these sectors and eventually impact macro-financial stability.

Resilience is an adaptive coping mechanism needed by health workers, especially nurses who have longer working hours than other health workers to provide care to patients in the era of the Covid-19 pandemic which is a global health problem. The aim of this literature review is to identify the resilience of nurses during the covid-19 pandemic the 21 st century global nursing paradigm. This language method uses literature reviews which are summaries of 10 articles in the publication years of 2020-2021 on search 4 databased electronic searches contain namely Scopus, ProQuest, Pubmed, and Scient Direct. This review used prisms. The eligibility of these studies were from its title, abstract, research methodology, results and discussion. The results of the review were presented in narrative form. The results of a review of 10 articles found that the form of psychological factors during the covid-19 pandemic, mental distress and influencing factors in nurses caring for patients with COVID-19, resilience nurses during the covid-19 pandemic. Conclusion: The 21 st century global nursing paradigm, one of the global problems in the health sector, with the outbreak of the corona virus disease (Covid-19), the role of nurses as the front guard is needed by the community to provide health services in line with the increasing incidence of covid-19 cases. Strong nurses need an adaptive inner coping mechanism.

Introduction: Corona Virus Disease 2019 causes health problems in the world in the form of a health crisis that results in psychological problems as fear and anxiety. The purpose of this study to determine the factors that influence psychological and stigma during the Covid-19 pandemic.Methods: This study is a literature review with five databases (Scopus, CINAHL, ScienceDirect, PubMed, and ProQuest), studies design used a cross-sectional or quasi-experimental, with a date of March 2021. The Center for Review and Dissemination and the JBI Guide are used to measure the Quality and Prism checklist for guide reviews. A feasibility study based on title, abstract, full text, and research methodology. The data analysis used narrative analysis based on the research findings.Results: Eleven articles met the predefined review inclusion criteria. Research is base on related factors psychology, related factors stigma, and factors related to psychological and stigma. Most of the factors associated with psychological conditions and stigma have a quasi-experimental and cross-sectional design. Participants averaged over a thousand for each study and discussed psychology factors related to the stigma. Conclusion: Factors related to psychological are age, education, symptoms and health conditions, gender, information, economy, exposure duration, and social support, while factors related to stigma are environment, history of comorbid diseases, discrimination, and public perceptions.

In critically ill patients with COVID-19, concomitant abnormalities of coagulation have been seen with an unusually high incidence. Standard coagulation tests are limited in their ability accurately to reflect the severity of the pro-thrombotic phenotype observed in severe COVID-19 infections. In this narrative review we consider the role of rotational thromboelastometry (ROTEM) as a near bedside test allowing a more comprehensive assessment of haemostatic function in the context of COVID-19 infection. Comprehensive literature search was conducted on PubMed, revealing 13 publications on the subject. The coagulopathy of this disease process appears to be insufficiently represented with often normal conventional coagulation test parameters. Whilst not the perfect substitute for in vivo coagulation, studies utilising rotational thromboelastometry assays in COVID-19 patients have demonstrated increased maximum clot firmness (consistent with hyper-coagulability) and reduced maximum lysis (consistent with “fibrinolytic shutdown”). ROTEM appears to be a possible tool for risk stratification and to monitor the potential modulation of fibrinogen-dependent coagulation processes with enhanced anti-coagulation strategies. Precisely how these coagulation abnormalities can be modified by optimum, individualised medical interventions to improve clinical outcome, however, remains unclear.

The Saudi government has undertaken rapid and swift actions, such as suspending Omrah and holding international flights. Such affirmative actions enhanced citizens and residents’ confidence in the government officials’ ability to fight the pandemic. However, there are more than 361,178 reported cases of Covid-19 with 6131 deaths as of December 22, 202. As nurses are the largest component of the health care workforce in Saudi Arabia, it is important that they are trained and have the skills and resources to adapt, whether on the frontline of a crisis or in a clinical environment. Nurses play a key function in fulfilling the needs of medical treatment by being the most important part of the health care delivery system.

Culture, gender and religion are closely linked each other’s, profoundly affect the role of each person within the Society, and also affect the ability to access to the health resources. We are now living a worldwide crisis due to the SARS-CoV-2 pandemic. In order to appropriately tackle it, an alliance between science, politics and citizens is needed. In this article, we summarize current evidences of how religions can represent, on one hand, a risk moment for spreading the virus (in relation with overcrowded events), on the other, a precious opportunity to engage people, and in particular minorities, in fighting the pandemic. To win this fight, we need a multicultural approach that takes into account every aspect of human life, and among these religion, which influences so much culture, everyday life and well-being.

Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).

Since the first confirmed case of COVID-19, information was spreading in large amounts over social media platforms. Information spreading about the COVID-19 pandemic can strongly influence people’s behavior. Therefore, identifying information superspreaders (or influencers) during the COVID-19 pandemic is an im- portant step towards understanding public reactions and information dissemination. In this work, we present an analysis over a large Arabic tweets collected during the COVID-19 pandemic. The presented study con- struct a network from users’ behaviors to identify information superspreaders during the month of March, 2020. We employed both HITS and PageRank algorithms to analyze the influence of information spreading, and compared the ranking of the users. The results show that both HITS and PageRank discovered a similar subset of superspreaders with 40% were found to be verified Twitter accounts.

Misinformation during the COVID-19 outbreak has shaped our perception of the disease. Some people thinkthe disease is a bioweapon while others are convinced that it is a hoax. Heightened anxiety often producesfearful rumors, some of which are absurd while others seem plausible and are laced with some truths. But, how does misinformation affect disease spread? In this paper, we construct a mathematical model parameterized by Ugandan data, to study the effect of misinformation on community COVID-19 spread. The analysis shows that misinformation leads to high number of COVID-19 cases in a community, and the effect is highest in the rumour initiators and spreaders. This analysis underscores the importance of addressing misinformation in COVID risk communication.

The infected and fatal cases of Coronavirus Disease 2019 (COVID-19) keep increasing around the world, to explore the infection routes and pathogenesis of 2019-nCoV could be meaningful for prevention and treatment of COVID-19. Previous studies showed that the oral cavity is at potentially high risk of 2019-nCoV infection. The ACE2 receptor of 2019-nCoV was reported could express on oral epithelium and salivary glands, and 2019-nCoV could be detected in patients’ saliva. Recently, the amblygeustia were found to widely exist in the COVID-19 patients. To explore the potential mechanism of amblygeustia, we performed further analysis via independent in-house single-cell profiles. Our results showed that ACE2 was inclined to express in taste cells, which indicated that 2019-nCoV may invade into taste cells at the early stage of COVID-19, and lead to the amblygeustia of patients. Above findings about the 2019-nCoV and COVID-19 in oral cavity are valuable and enlightening for future epidemic prevention strategy.

We have proposed a model considering two equally sized population (group A and group B) with low and high levels of disease tolerance. We have argued that in the more tolerant group (group B) the progression of the disease with respect to time will be slow with lower number of infections at any given time. We attribute this effect to the innate immunity which advantageously, can also be one of the major contributing factors for flattening the curve. We have compared the growth of Covid-19 disease in various countries to understand this effect.

The COVID-19 pandemic spread of the coronavirus across the globe has affected our lives on many different levels. The world we knew before the spread of the virus has become another one. Every country has taken preventive measures, including social distancing, travel restrictions, and curfew, to control the spread of the disease. With these measures implemented, people have shifted to social media platforms in the online sphere, such as Twitter, to maintain connections. In this paper, we describe a coronavirus data set of Arabic tweets collected from January 1, 2020, primarily from hashtags populated from Saudi Arabia. This data set is available to the research community to glean a better understanding of the societal, economical, and political effects of the outbreak and to help policy makers make better decisions for fighting this epidemic.

The pharmacology of azithromycin, and the actions of certain bee products, suggest the possibility of overlap with the pathophysiology of COVID-19 at several points in the disease process. First, intercellular epithelial tight junctions of the respiratory tract serve as a critical barrier to invaders. Pathophysiological factors capable of disrupting this epithelial barrier include viral virulence factors such as those observed for other coronaviruses; virulence factors derived from potentially synergistic pathogens such as Candida albicans and Porphyramonas gingivalis; and imbalances in the host inflammatory response. Azithromycin, and to a lesser extent, certain bee products, appear to have actions that oppose such processes. Second, the matrikine PGP or its derivatives may contribute to risk in individuals at high risk for serious COVID-19 infection, especially during reactivation; but azithromycin is capable of modulating PGP in some contexts. Third, the most serious COVID-19 infections are associated with massive upregulation of inflammatory cytokines such as IL-6, TNF alpha, and other inflammatory cytokines. The anti inflammatory actions of azithromycin and bee derived products such as melittin are potentially capable of modulating these processes, as well. Azithromycin is already in current use as a treatment for COVID-19; however, it's utility as a protector of epithelial barrier function would be most likely to be realized in prophylactic context rather than in a treatment context. Similarly, since the anti inflammatory effects of bee products take time, their effectiveness of melittin and other bee products would be expected to be maximized in a prophylactic context. In the context of the current pandemic, prophylaxis with azithromycin, bee products, or both, might be warranted for individuals at high risk for serious COVID-19 infection.

Novel coronavirus (COVID-19) can lead to multiple organ injuries such as acute respiratory distress syndrome (ARDS), acute renal injury (AKI) and so on. ACE2 is an important part of the renin-angiotensin system (RAS) and a key protein needed for COVID-19 to invade cells. First of all, we searched the HPA, GTEx and FANTOM5 Databases and found that the expression of ACE2 in kidney tissue was significantly higher than that in lung tissue. Then, by searching the Nephroseq Database, it is further verified that ACE2 is highly expressed in renal tissue and plays a protective role in renal tissue. However, current studies have found that the incidence of AKI caused by COVID-19 is much lower than that of ARDS. Because of this, we further searched the proteins interacting with ACE2 protein through the STING Database and analyzed the expression of tissue protein mRNA in the HPA Database. It was noted that AGTR2 mRNA was highly expressed in lung tissue, but low in kidney tissue, and hard tissue specificity in lung tissue. Through further research, it is found that AGTR2 plays a major role in the development of pulmonary fibrosis. Therefore, AGTR2 may be a key protein in COVID-19 pneumonia, and AGTR2 may be a potential new therapeutic target for the treatment of COVID-19 patients.

Myocarditis has been recognized as a possible rare complication of COVID-19 mRNA vaccination. It concerns between one and five vaccinated people per 100,000 in the general population, with increased incidence in adolescent and young adult men. Most often, cases of myocarditis have been reported in the days following the second dose of vaccine mainly in younger male patients. This rare complication of vaccination usually resolves within days or weeks. However, the pathophysiological events responsible for the increase in frequency of myocarditis after COVID-19 vaccination remain unclear. Several recent reports have highlighted that free spike proteins circulating in the blood of patients at high levels appear to play a major role in myocarditis. Here, we review the most relevant data that partly lift the veil on the molecular mechanisms of the induction of myocarditis following mRNA-based COVID-19 vaccination. We hypothesize that a mechanism of molecular mimicry of the viral spike triggers transient dysregulation of angiotensin-converting enzyme 2, leading to increased soluble angiotensin II binding to the transmembrane receptor angiotensin II type I receptor, similar to what is observed during SARS-CoV-2 infection. We suggest to standardize management of suspected cases of mRNA-based COVID-19 vaccine-induced myocarditis, including angiotensin II and spike antigenemia monitoring.

Similarly to a phoenix, SARS-CoV-2 has appeared periodically in waves. The new variants that appeared through mutations have during the 4 years of the pandemic suppressed earlier variants, causing new waves of the pandemic. The Omicron BA.2.86 Pirola variant is the latest in the sequence of SARS-CoV-2 variants, which appeared in 2023. The BA.2.86 variant has started to spread rapidly and we are witnesses of a new epidemic wave. In this short period, an increased infectivity was noticed, which results in rapid spreading and decreased pathogenicity, which results in a lower number of severe cases. However, in the public there is a fear of further development of the epidemic. This analysis was made with the goal to assess the risks in the period of late 2023. Mutations that were developed by the BA.2.86 variant have led to a change in empirical formula and thermodynamic properties. It seems that there is no ground for fear of an extensive spreading of severe forms, but there are reasons for caution and monitoring of the spreading of the epidemic and potential appearance of new mutations.

Long COVID comprises persistent symptoms which extend beyond four weeks post-SARS-CoV-2 infection. The potential association between long COVID and the endorsement of COVID-19 conspiracy theories has not been explored, particularly in Arab countries where high endorsement of these theories has been reported. This study aimed to explore the association between endorsing COVID-19 conspiracy theories and the prevalence of self-reported long COVID symptoms among adults in Jordan and Kuwait in addition to other Arab countries. The study employed a cross-sectional design using an electronic self-administered survey in Arabic language. Recruitment utilized snowball sampling via social media and the survey was distributed in July 2024. The survey instrument included sections on demographic information, the history of COVID-19 infection, and vaccination status. Long COVID manifestations were assessed using a score reflecting the frequency and intensity of ten recognized long COVID symptoms with subsequent categorization into three categories: low, middle, and high. The beliefs in COVID-19 conspiracy theories were measured via a 5-point Likert scale across five items. The final study sample comprised 756 respondents, the majority of whom self-reported a history of confirmed COVID-19 diagnosis at least once (n = 493, 65.2%). The results indicated a neutral average attitude towards COVID-19 conspiracy theories (mean score = 15.18±4.64 out of 30.00). Participants with high conspiracy theories scores were significantly more likely to report high (aOR = 6.85, 95% CI: 2.90–16.13, p &lt; 0.001) and middle long COVID symptoms (aOR = 2.82, 95% CI: 1.32–6.06, p = 0.008) compared to those with lower scores. Additional predictors of higher long COVID reporting included female sex and lower self-reported household income. Frequent COVID-19 infections and hospitalizations were also associated with higher long COVID symptom reporting. The study results revealed a significant correlation between the endorsement of COVID-19 conspiracy theories and the higher frequency and magnitude of long COVID symptom reporting. The findings also highlighted the influence of sociodemographic factors and COVID-19 infection history on long COVID reporting, which suggests that public health strategies should address these factors to mitigate long COVID challenges effectively.

COVID-19 pandemic disproportionately affected seven South Asian countries because of rampaging virus and weak health system response. Vaccination commenced in all countries during early 2021, once the vaccines became available in the international market. Vaccines were donated by international development partners, friendly countries and procured utilizing domestic resources and financial support from various agencies. All countries opted for a phasing of the vaccination by prioritizing high risk populations which included health care personnel, front line workers and elderly with comorbidities. Seven vaccines that had WHO emergency authorization usage were utilized in South Asia. India produced more than 2.4 billion doses of AstraZeneca vaccine and has indigenously developed five COVID-19 vaccines. Vaccine inequity was obvious and characterized by fewer people in South Asia vaccinated with single dose vis a vis the developed countries. Vaccine hesitancy was another obstacle that kept the vaccination rates low. Difficult to reach areas in Afghanistan, Bhutan, Maldives, Nepal could not fully access vaccines. South Asian countries need to strengthen their health system for efficient deployment of vaccines in future health emergencies. At the same time the global agencies and developed countries must address the issue of vaccine access to low-income countries to mitigate the impact of pandemic all over the world.

Coronavirus 19 disease (COVID-19) may be complicated by thrombotic events, particularly venous thromboembolism (VTE), which have been reported both in critically ill hospitalized patients and in individuals with mild symptoms. It is known that the chronic use of oral contraceptive pills (OCPs) is associated with higher risk of VTE. To date, there are only few reports concerning the association of OCPs and VTE/pulmonary embolism (PE) in COVID-19 patients. Given that during the convalescent phase of disease, a state of endothelial dysfunction, hypercoagulability and a low-grade inflammation may be persistent, the occurrence of thromboembolic events following acute COVID-19 infection may be not surprising. Herein, we report a case of high-risk PE detected in a post-COVID-19 young woman under hormonal contraception, which required thrombolytic treatment. A number of prothrombotic phenomena, such as overweight, hormonal contraceptive therapy, recent COVID-19 infection and prolonged immobilization, might have synergically contributed to the development of a sublethal thromboembolic event.

The prevalence of corona virus and the novel COVID-19 disease in the entire globe has exacerbated different impact on socioeconomic spectrum in the world, including water use pattern. Thus a research was conducted to examine the comparative use of water during pre- and post-COVID-19 lockdown pattern among post-primary schools in Iwo, Osun State, Nigeria. A survey was conducted among fifteen schools which were randomly selected, but with eight public and seven private schools for the investigation. Both descriptive and inferential statistical techniques were used in data analysis. The results revealed that the major source of water to the schools investigated is ground water which is obtained through hand-dug wells and boreholes. It was further discovered that there was increase in water use during post-COVID-19 lockdown era as a result of the directive by the government that clean water should be provided for hand-washing by all schools regardless of the owner to curtail the spread of COVID-19 disease in the country. One sample t-test also revealed that there was a significant difference in water use at (p<0.01) level. It is recommended that the government and other stakeholders in water sector to ensure that all-time and non-seasonal dependent source of water be provided rather than ground water source which is susceptible to variations in water yields from seasonal variations. This will enable continuous clean water supply, for all purposes, including COVID-19 protocols.

The aim of the article is to determine the predictors of mental health among Polish society. Research was conducted after the first wave of the pandemic. Due to such an approach, it was possible to determine whether secondary effects of the pandemic have impact on mental health, apart from socio-demographic and psychological factors. In order to gather the research material, the CAWI on-line survey method was applied and carried out within the framework of the Ariadna Research Panel on the sample of 1079 Poles aged 15 and over. The FCV-19S scale, which is used to measure the fear of COVID-19 was applied in the measurement. It is a verified diagnostic instrument used to measure mental health in a lot of countries. The results of a hierarchical regression analysis have shown that the factors which increase the level of fear of COVID-19 are demographic, social and psychological features as well as attitudes towards the pandemic. The results of research indicate the significance of social context in the analysis and explanation of the effects of disasters and cataclysms.

Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.

Objectives to assess COVID-19 mortality rates per country population. To determine what if any independent country-specific variables from 9 different databases were correlated. Design population based retrospective cohort study. Setting analysis of global COVID-19 treatment and containment strategies using data from 9 worldwide websites. Participants 108 countries worldwide. Interventions none. Main Outcome Measures were COVID-19 death rates per country population analyzed by univariate and multivariate analysis. The main outcome parameters were to determine if there are any correlations between the percentage of countrywide COVID-19 deaths/population by the countries’ percent vaccinated. Secondary outcome measures include the effect of other independent variables on COVID-19 death rates per country population including: health expenditures per capita, annual income per capita, COVID-19 tests per 1000 people, stringency index (a measure of each countries containment strategies), hydroxychloroquine score (a measure of each countries use), ivermectin score (a measure of each countries use), hypertension, obesity, diabetes, and specific countries and geographic locations. Results COVID-19 vaccination rates ranged from 0-99% in 108 countries. Univariate analysis demonstrates the following independent variables to correlate with COVID-19 deaths/population (correlation coefficient, p value): countrywide COVID-19 vaccination rates (+0.2936, p=0.002); healthcare costs per capita (+0.3212, p=0.0007), income per capita (+0.3051, p=0.0013), COVID-19 tests per 1000 population (+0.6981 p=0.0307); stringency index (+0.3098, p=0.0011); hydroxychloroquine index (-0.1337, p=0.0678); and ivermectin index (-0.1383, p=0.1535). Conclusions Increasing rates of COVID-19 vaccination are associated with increase COVID-19 death rates per country population (p=0.002). Other variables associated include healthcare costs per capita (+0.3212, p=0.0007), income per capita (+0.3051, p=0.0013), COVID-19 tests per 1000 population (+0.6981 p=0.0307); and stringency index (+0.3098, p=0.0011).

Human-to-animal SARS-CoV-2 transmission was observed, including a veterinarian contracting COVID-19 through close contact with an infected cat, suggesting an atypical anthropozoonotic transmission. This study investigated the prevalence of SARS-CoV-2 antibodies in cats during human outbreaks and elucidated the correlation between cat infections and human epidemics. A total of 1,107 cat sera samples were collected and screened for SARS-CoV-2 antibodies using a modified indirect ELISA human SARS-CoV-2 antibodies detection kit. The samples were confirmed using a cPass surrogate viral neutralization assay. The SARS-CoV-2 seropositivity rate was 22.67% (199/878), mirroring the trend observed in concomitant human case numbers. The waves of an epidemic and provinces did not significantly impact ELISA-positive cat. Notably, Chon Buri ex-hibited a strong positive correlation (r = 0.99, P = 0.009) between positive cat sera and reported human case numbers. Additionally, cPass surrogate viral neutralization revealed a 3.99% (35/878) seropositivity rate. While there were significant differences in positive cat numbers and proportions between epidemic waves. In Samut Sakhon, a positive correlation (r = 1, P = 0.042) was noted between the proportion of positive cat sera and reported human cases. The findings emphasize the need for ongoing surveillance to comprehend SARS-CoV-2 dynamics in both human and feline populations.

Background: Since the previous study dealing with the case fatality ratio and infection fatality ratio caused by COVID-19, the author has received many comments that prompted the question: "Why did an optimistic prognosis fail?" To answer this question, a more detailed and expanded analysis was carried out in a new study. Objective: To evaluate the dynamics of monthly numbers of cases, deaths, tests and CFR worldwide during three phases of the COVID-19 pandemic. Material and Methods: Twenty three sets of databases, dated the 22nd of each month from January 2020 to November 2021, for 213 countries were collected from the Worldometer website. The number of cases, deaths, tests, CFR, IFR, etc. were counted for various periods of time for each of the 213 countries, then results related to different periods of time were compared. Results: The analysis of the main epidemiological parameters led to the division of three phases of the global pandemic evolution. The first phase (23.01.20-22.07.20), the second phase (23.07.20-22.01.21) and the third phase (23.01.21-22.07.21) were different in terms of the number of tests performed, new cases, and mortality due to COVID-19. By the end of the second phase, the worldwide statistics indicated the imminent end of the pandemic, but the third phase was characterized by a sudden rise in the number of new cases and deaths that could not be explained rationally. The most dramatic evolution of the epidemic curve occurred in the countries where doctors had successfully battled COVID-19 during the first two phases of the pandemic. Conclusions: Despite the decrease in overall death numbers during the latest months analyzed, additional study is necessary to identify the cause for the increase in the number of new cases and deaths during the third phase of the pandemic. Only complete information regarding the positive and negative impact of medical and non-medical methods of diagnostics and prophylaxis of COVID-19 can help to organize effective measures to end the current pandemic and prevent a similar one from occurring in the future. Presumably, there are several causes of the negative evolution of the current pandemic, including the overreliance on PCR tests, application of non-specialized premises for quarantine and treatment, decrease in herd and individual immunity, inadequate change of therapeutic protocols, and ignoring prophylactic treatment. It can be suggested that the use of immunemodulatory drugs, for example, thymus extract or thymic peptides, in groups of people with compromised immunity is necessary, and prophylactic and therapeutic protocols should be changed from the 'standard' types to 'personalized' ones.

The coronavirus disease 2019 (COVID-19) was officially declared a pandemic on the 11^th March 2020. It is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), impacting the lower respiratory tract. International travel to Australia during the early stages of the pandemic prior to border closure provided avenues for this virus to spread into Australia. There is little understanding of the clonality of SARS-CoV-2 isolates in Australia, and where they originated. This study aimed to investigate the clonality and ancestral sources of SARS-CoV-2 isolates in Australia using in silico methods. We retrieved 1,346 complete genomes from Australia along with 153 genomes from other countries from the NCBI nucleotide database and Global Initiative On Sharing All Influenza Data (GISAID). We then constructed a representative population of 270 sequences for downstream phylogenetic analysis and ancestral area reconstruction. Overall, two major clusters, one stemming from Europe and another from Asia, especially East Asia, were observed, implying at least two major transmission events with subsequent clades confirming the multiclonality of Australian isolates. We also identified three potential dissemination routes of SARS-CoV-2 into Australia. This study supports the hypothesis of multiple clonality and dispersals of SARS-CoV-2 isolates into Australia.

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation Results: a total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19 +), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS CoV-2 (-) negative lungs (COVID-19 -), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1 positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes over-expression in the lung. Conclusions: microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

SARS-CoV-2 infection remains a global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood including the kinetics of formation of genomic RNA (gRNA), sub-genomic RNA (sgRNA) and replication centers/organelles (ROs). We employed single-molecule RNA-fluorescence in situ hybridization (smRNA-FISH) to simultaneously detect viral gRNA and sgRNA, immunofluorescence to detect nsp3 protein, a marker for the formation RO, and carried out a time course analysis. We found that single molecules of gRNA are visible within the cytoplasm at 30 minutes post-infection (p.i.). Starting from 2 hr. p.i., most of the viral RNA existed in clusters/speckles, some of which were surrounded by single molecules of sgRNA. These speckles associated with nsp3 protein starting at 3 hr. p.i., indicating that these were precursors to ROs. Furthermore, RNA replication was asynchronous as cells with RNA at all stages of replication were found at any given time point. Our probes detected the SARS-COV-2 variants of concern, and BA.1 strain exhibited slower rate of replication kinetics than the WA1 strain. Our results provide insights into the kinetics of SARS-CoV-2 early post-entry events, which will facilitate identification of new therapeutic targets to early stage replication to combat COVID-19.

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against ancestral and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5 and XBB.1.5) in human serum. For ancestral strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity. The assay was robust against changes to virus/serum incubation time, cell seeding density, virus content per well, cell passage number, and serum interference. Analyte in serum samples was stable up to 5 freeze/thaw cycles and for up to 12 months of storage at –80 ± 10 °C. Similar results were observed for the variant-adapted MN50 assays. The conversion factor to convert assay result units to WHO international standard units (IU/mL) was determined to be 0.62 for the ancestral prototype strain. This MN50 assay will be useful for vaccine immunogenicity analyses in clinical trial samples, enabling assessment of vaccine immunogenicity for ancestral and variant strains as variant-adapted vaccines are developed.

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

To better understand the genes with altered expression caused by infection with the novel coronavirus strain SARS-CoV-2 causing COVID-19 infectious disease, a tensor decomposition (TD)-based unsupervised feature extraction (FE) approach was applied to a gene expression profile dataset of the mouse liver and spleen with experimental infection of mouse hepatitis virus, which is regarded as a suitable model of human coronavirus infection. TD-based unsupervised FE selected 134 altered genes, which were enriched in protein-protein interactions with orf1ab, polyprotein, and 3C-like protease that are well known to play critical roles in coronavirus infection, suggesting that these 134 genes can represent the coronavirus infectious process. We then selected compounds targeting the expression of the 134 selected genes based on a public domain database. The identified drug compounds were mainly related to known antiviral drugs, several of which were also included in those previously screened with an in silico method to identify candidate drugs for treating COVID-19.

During COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Basing on previous data on Methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly associated to the intrinsic antimetabolic activity of these drugs, but also to a specific antiviral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, Pralatrexate and Trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.

Abstract Introduction: Long COVID (LC) affects multiple systems and has a significant health impact on patients and society. Therefore, long COVID services should address patients’ needs through a holistic assessment and monitoring of patients’ symptoms. Aim: The aim was to understand which of the symptoms were most and least likely to improve, after our rehabilitation intervention so that the rehabilitation measures in the clinic could be modified to meet patients’ needs. At the same time, we wanted to assess the feasibility of using C19-YRS ELAROS application in monitoring of LC symptoms during and after the rehabilitation clinic attendance. Methodology: In this study, a total of 50 patients who have attended long COVID rehabilitation clinic in Salford, UK; were assessed by using digitalised C19-YRS ELAROS application. A total of 100 eligible initial and final post rehabilitation assessments were analysed. Conclusion: Pain and anxiety symptoms were the two most likely symptoms to improve after intervention at LC rehabilitation clinic, whereas swallowing difficulty is least likely to improve. Issues with caring for family/ social life (symptoms affecting social role) are likely to worsen even after treatment. It is feasible to monitor and track Long COVID symptoms utilising the digitalised version of C19-YRS via the ELAROS App. This also allows the tracking of symptoms overtime.

Cross-sectional survey was conducted to capture the true extent of COVID-19 exposure among students and staff of Polytechnic High School (PHS). Random cluster sampling was carried out between May 19 and August 18, 2022, after the fourth wave of COVID-19 transmission. IgM and IgG SARS-CoV-2 antibodies were screened using WANTAI SARS-CoV-2 ELISA assays. Seroprevalence and descriptive statistics were calculated. Moreo-ver, the association between seropositivity and different factors (age, gender, preventive measures comorbidity, and symptoms, etc.) was determined using Logistic Regression. The overall IgG and IgM seroprevalence were 92% and 6.91% respectively. We found a higher IgM seroprevalence in men than women (9.4% vs. 5.6%) and a lower IgM seroprevalence in (18-25) age group compared to (55-65) years. Low compliance with preventive measures was found with a significant IgM seroprevalence depending on non-respect of social distancing (p = 0.008). A total of 70% of participants presented symptoms linked to COVID-19 at the moment of the survey. Results revealed a significant difference according to IgG seroprevalence among participants who declared fa-tigue symptoms 92.06% compared to those who did not 80.39% (p = 0.0027). IgM seropositivity was associated with Body Mass Indice (BMI) categorized (O.R. 0.238, p = 0.043), ethnic group (O.R. 0.723, p = 0.046) and marital status (O.R. 2.399, p = 0.021). Moreover, IgG seropositivity was associated with Chronic sinusitis comorbidity (O.R. 0.238, p = 0.043) and vaccination status (O.R. 4.741, p < 0.001). The majority of students and staff have al-ready been exposed to SARS-CoV-2 and confirm the circulation of SARS-CoV-2 in PHS at the time of the survey. Our results underline the importance of sero-epidemiological surveys to estimate the real impact of the COVID-19 pandemic in a community and to monitor disparities in antibody response in the population.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we report the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and correctly processed and transported to the cell surface, where it efficiently produced cell-cell fusion. Version Spf, however, was not proteolytically processed and despite being transported to the plasma membrane, it failed to induce cell-cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin converting enzyme 2 (K18-hACE2) mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the levels of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

Understanding how the coronaviruses invade our body is an essential point, and the expression profile of coronaviruses receptor may help us to find where the coronavirus infects our body. We found that the coronavirus receptors, including angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-Cov-2, are digestion-related enzymes in human enterocytes. Coronaviruses are continually altering the binding receptor and binding modes during their evolution, but the potential target cell in the small intestine is constant when in the lung is inconstant. Enterocytes may act as a conserved cell reservoir for coronaviruses, which may be partially explained by the Red Queen hypothesis. We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies.

Cancer patients, susceptible to severe COVID-19 outcomes, exhibit varied vaccine responses, particularly those who are receiving chemotherapy. This prospective cohort study enrolled 115 cancer patients, and data from 91 patients who received two doses of COVID-19 vaccines were analyzed. Blood was drawn at baseline, day 28, and 6 months post-second dose for neutralizing antibody analysis. The primary outcome was seroconversion rate against wild type and Omicron at day 28. Secondary outcomes included seroconversion at 6 months, factors associated with seroconversion, and safety. Of the 157 cancer patients screened, 91 were enrolled, with 45% receiving chemotherapy. Seroconversion rates at day 28 were 77% for the wild type and 62% for Omicron. Chemotherapy did not affect seroconversion (p=0.789 for wild type, p=0.597 for Omicron). Vaccine type positively correlated with seroconversion, with an adjusted ORR of 25.86 (p=0.029) for the wild type and 17.38 (p<0.001) for Omicron with the primary heterologous vaccine. Adverse events were grade 1 in 34.0% and grade 2 in 19.7% of participants. Despite lower seroconversion against Omicron, no difference was noted between chemotherapy and non-chemotherapy groups. COVID-19 vaccinations demonstrated good tolerability. This data underscores vaccine efficacy considerations in cancer patients, informing tailored strategies for this vulnerable population.

This study focuses on cardiovascular effects, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students from two schools aged 13–18 years who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms.We enrolled 314 participants; of these, 13 participants were lost to follow up, leaving 301 participants for analysis. The most common cardiovascular effects were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular effects were found in 29.24% of patients, ranging from tachycardia, palpitation, and myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. Conclusion: Cardiovascular effects in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myocarditis. The clinical presentation of myopericarditis after vaccination was usually mild, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for side effects. Clinical Trial Registration: NCT05288231

Objectives: This study aimed to analyze the awareness of local residents regarding healthcare projects and to suggest some ideas for the revision of local ones. Methods: To delve into the opinions of local residents, the author of this study created a questionnaire composed of eight questions on the general characteristics of the respondents, eight questions on satisfaction with health centers, 16 questions on the awareness of healthcare projects, and 22 questions on local healthcare. The survey was conducted for 409 residents who visited public centers in Gimcheon from 15 March to 14 April 2021. Results: Data analysis revealed the following: The proportion of local residents who use health centers was 39.1%, and those users visit health centers, on average, 3.92 times a year. Among healthcare projects, the project known by the highest proportion of people was vaccinations (84.5%), which was also the project that was most used (38.1%). Among healthcare projects needed in the with-COVID-19 age, respondents awarded the highest score to vaccinations (4.15 points on a five-point Likert scale) and the second highest score to infectious disease management (4.12). Conclusions: For healthcare projects, central and local governments should focus on activating vaccinations, solving the problem of medical accessibility through untact remote treatment and establishing national infectious disease-specializing hospitals and local infectious disease management based on such national hospitals.

The global spread of coronavirus disease (COVID -19) worldwide has had a significant effect on social and economic growth. The contamination keeps on advancing quickly and eccentrically, representing a significant test to its recognition and conclusion. Coronaviruses are commonly recognized by seclusion from tests, regardless of whether natural or clinical, utilizing some atomic science procedures, which can take a few days. In this work an analytical review of virus transmission, methods of diagnosing COVID -19 using artificial intelligence techniques to classify images and types of biosensors. At long last, the deformities and points of interest of each kind of sensor are recognized and examined. This exploration gives an explanatory audit of the utilization of crown infection COVID-19 in 2019. Related examinations were led utilizing five dependable databases, for example, Science Direct, IEEE Xplore, Scopus, Web of Science, and PubMed. An acceptable investigation is remembered for this audit, which can be depended upon as a logical database to put resources into another technique for recognizing COIVD-19.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

Draconian defensive measures have been implemented to combat the COVID-19 pandemic outbreak. These important measures constitute a vital current priority but do little to increase communal immunity and avoid future outbreaks. A longer-term exit strategy for a sustainable return to normalcy has yet to be identified. The development of vaccines or effective therapeutics could largely solve the problem, but their timely development cannot be guaranteed. In this setting, and under the expected societal isolation fatigue from extended social distancing, we here propose the idea that at some point after the outbreak’s peak, hospitals, in addition to providing care for infected people who need it, could also be involved in the development of a controlled exit strategy designed to avoid future outbreaks. We postulate that controlled voluntary deliberate infection in a hospital setting and under continuous and close medical observation may offer a safer alternative compared to random en-masse exposure. We discuss potential risks and benefits, highlighting the need for careful consideration of the associated critical ethical issues.

Abstract: This brief policy is written after experience treating COVID-19 positive radiation therapy patients to reduce risk to therapy staff and patients in radiation oncology department. It is important to prioritize the safety of staff and non-infected patients while ensuring the continuation of radiation oncology services. Radiation therapists have sustained contact with covid-19 patients in an enclosed vault. Protocols for correct disinfecting of equipment and room and therapists following methods for less transmission of virus is crucial. This policy covers prevention methods from COVID-19 transmission from patient to patient, patient to staff, staff to patient and staff to staff as follows A.Risk reduction by screening and preparing staff and rooms B.Radiation Therapist Policy for COVID-19 positive patient with CCC (Critical Cancer Care)

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global threat to human health and disease risk increases with advancing age. The regulation of the ACE2 gene that codes for COVID-19 host receptor ACE2 has been shown to be under epigenetic regulation. Here, we examined whether intensive DNA methylation profiling of the ACE2 gene differed by human host tissue and cell type, gender, and age. Results: Accessing four public datasets, we observed unique human cell-type-specific ACE2 DNA methylation patterns. In human lung tissues, gender differences in DNA methylation at 2 sites related to the ACE2 gene were identified. Further, in freshly isolated airway epithelial cells, DNA methylation near the transcription start site of the ACE2 gene associated with biological age. Conclusion: Epigenetic profiling of host tissue may permit discovery of age and gender-related potential risk factors for COVID-19. How perturbations in ACE2 methylation relate to clinical severity across the ages and gender needs to be determined to guide screening tools and potential epigenetic modification targeting to alleviate COVID-19 morbidity in the elderly.

Quinine and its less toxic derivatives have served humanity for decades as potent antimalarial drugs. Emergence of drug resistance has narrowed the usage of these drugs in malaria prevention and treatment. Fortunately, these drugs have roles in the treatment of other diseases as well including rheumatic disorders and viral infections. Quinine derivatives have proven antiviral effects, especially against human immunodeficiency virus (HIV), Zika virus (ZiKV), herpes simplex virus (HSV), Ebola virus and dengue virus (DENV). The prophylactic and therapeutic role of Chloroquine/hydroxychroquine has become a topic of interest after the recent outbreak of novel Corona virus-19 (nCoV-19). This virus is also named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and WHO has officially named this disease as Corona virus disease 2019 (COVID-19). This lethal virus has affected almost 186 countries of the world till to date just in a period of four months of its outbreak. No approved antiviral drug is existed for the treatment of COVID-19. Therefore, this review is focused on potential prophylactic and therapeutic role of chloroquine/hydroxychlroquine for COVID-19.

The product is a centrifugal air extractor, whose objective is to extract the stale air of SARS-CoV-2 or Covid-19 (Coronavirus); designed for civil and commercial use, it works with a single-phase alternating current (AC) motor of 220 (V) and 50 (Hz), with high energy efficiency (EE). Developed under the Design Thinking methodology, by electromechanical simulation using NI Multisim 14.0 software, case design using Cfturbo 2020 R2.0 CAD software, and rapid 3D prototyping with the OverLord Pro printer; with a prototype of the conventional stator winding of a synchronous motor with a two-pole PMSM/IPM single-phase alternating current (AC) field winding and a 4000 (Gauss) ferromagnetic ceramic magnet rotor. Innovating online nº 15 of invention patent nº 381968 by Nikola Tesla, 5/1/1888.One of the objectives is to link the middle level or Technical Schools with the University system (and careers with a Technological profile) through Project B374 located in the Secretariat of Science and Technology (SCyT) of the National University of La Plata ( UNLP), whose title is: “Integrated Management of Design and Innovation. Contributions for a theoretical-conceptual and methodological review” by the Director: Mg. Federico del Giorgio Solfa. Just as links were sought with the Research and Development Laboratory of the Department of Industrial Design (LIDDI-FBA-UNLP) through its Director D.I. Pablo Ungaro and D.I. Ana Bocos. In 2021, the project participated in the INNOVAR National Contest of the Ministry of Science, Technology and Productive Innovation of the Nation (MINCYT), Argentine Republic; in the "Covid-19 Projects" category, having been selected in the catalog of innovative products, won the 1st. "Covid-19 Projects" position of the National Agency for Research and Technological Development and local innovation (R+D+i) dependent on MINCYT.The results showed, according to the analysis of the test bench, that the PMSM/IPM type synchronous motor used in the centrifugal fan, with the innovation of the reactance-inductive control in series plus the capacitor in parallel, reduces the power by 67% (Watts) and active energy consumption (kWh), performing 56% more mechanical work (Joules) on the fluid air (with a 50% reduction in carbon footprint). Which leads us to the following conclusion: it is possible to develop centrifugal fans that save electricity (kWh) without the need to resort to (1) the "Fan Affinity Law", nor (2) the use of variable speed drives (VDF) or frequency (which are devices with complex and expensive electronics). Which would bring an enormous saving of the cost of electrical energy.

Abstract: The objective of this meta-analysis was to evaluate the factors associated with mortality of elderly Italians diagnosed with the new coronavirus who resided in institutions or who were hospitalized as a result of the disease. Methods: A systematic review following the recommenda-tions of The Joanna Briggs Institute (JBI), where the PEO strategy was utilized - Population, Exposure and Outcome. P, being the elderly over 65 years old. E, the SARS-CoV_2 pandemic. O, mortality. The NCBI / PubMed, LILACS, EMBASE and CINAHL databases were used until July 31, 2020.; Results: Five Italian studies were included in the meta-analysis, with the number of elderly people varying between 18 and 1591 patients. The main morbidities presented by the elderly in the studies were: dementia, diabetes, chronic kidney disease and hypertension. Conclusions: The factors as-sociated with the mortality of elderly Italian people diagnosed with SARS-CoV-2 who lived in in-stitutions or who were hospitalized because of the disease were evaluated. It was found that de-mentia, diabetes, chronic kidney disease and hypertension are the main the main diagnosed dis-eases for mortality in elderly people with Covid-19.

Background: Chronic neurologic diseases are common sequelae of COVID. They severely impact the quality of life and increase the burden on healthcare systems. The long COVID neurological symptoms are due to the robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to neuroinvasion and inflammation of the central nerve system (CNS). Currently used medications and vaccines do not inhibit the robust SARS-CoV-2 replication in the nasal epithelial cells. EGCG-palmitate (EC16), a multifunctional compound, has the potential to become a novel intranasal-delivered drug for minimizing post-COVID neurologic symptoms. Method: EC16-containing formulations were developed and tested in vitro against human β coronavirus OC43 (CoV-OC43) using a TCID50 assay following three test protocols differing in exposure sequence. Results: EC16 formulations in normal saline, phosphate buffered saline, and cell culture medium were found to effectively inhibit human β-coronavirus infection (&gt;99.99%) after a 30-min contact. A single 10-min application to cells after infection (i.e., without direct contact with the virus) resulted in &gt;99% inhibition of viral replication. Conclusion: With its antiviral, antioxidant, anti-inflammatory, and neuroprotective properties, EC16 in nasal formulations could be further developed for clinical applications to COVID-19 patients for minimizing long COVID neurological symptoms.

This study is a cross-sectional survey involving physicians around Indonesia aimed to explore physician hesitancy to treat COVID-19 patients after experiencing COVID-19 infection coupled with associated occupational risk factors. The questionnaire was distributed via contact information from the Indonesian Physician Association database. Out of 383 participants, 25.6% suffered from moderate symptoms of COVID-19 and 2.9% were admitted for critical care. Hesitancy to treat suspected, probable, or confirmed COVID-19 patients was found in 20.3% of physicians. A higher hesitancy rate was found in older physicians and those with less experience in treating COVID-19 patients. Specialist trainees and those who work in public hospitals were physicians with the lowest hesitancy in treating COVID-19 patients. There is a significant hesitancy in treating COVID-19 patients among physicians who have suffered from COVID-19 which calls for further action by management and policy makers.

Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread among the population. Aim: to study the evolution of SARS-CoV-2 humoral immunity in the Belarusian population relative to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing population immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health with the participation of the St. Petersburg Pasteur Institute (SPPI), taking into account WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by questionnaire using a cloud (internet server) service. To monitor population immunity, a cohort of 4,661 people (participating in all stages of seromonitoring) was formed from the overall volunteer group. Volunteers were randomized by age group (1-17, 18-29, 30-39, 40-49, 50-59, 60-69, 70+ years), region, and professional group. For the detection of antibodies (Abs) to nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), corresponding assay systems were used following manufacturer instructions. The study was conducted in 4 stages according to a single scheme. Results. In the 1st stage (pandemic month 15), collective immunity was due mainly to Nc+RBD+ Ab status alone. By the 2nd stage (carried out after 4 months), their share decreased 1.2-fold, while the share of volunteers who had only RBD Abs increased 1.7-fold. In the 3rd and 4th stages (carried out after 9 and 19 months), the share of persons with RBD+Nc‒ compared to the 2nd stage decreased by 3.5%; the proportion of persons with Nc+RBD‒ Abs increased by 1.5-fold. The most important factor in population immunity was vaccination of the population, the coverage of which reached 70% by the 4th stage. Among vaccines, the Sputnik V and Sputnik Light vector designs were used most often. The whole-virion, inactivated BIBP-CorV vaccine was used less often. Conclusion. The evolution of collective SARS-CoV-2 humoral immunity included a set of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence to nearly zero.

RNA viruses exhibit a great tendency to mutate. Starting from 2019, the wild type that was labeled Hu-1 has during the last 3 years evolved to produce several dozen new variants, as a consequence of mutations. Mutations cause changes in empirical formulas of new virus strains, which lead to change in thermodynamic properties of biosynthesis and binding. These changes cause changes in the rate of reactions of binding of virus antigen to the host cell receptor and the rate of virus multiplication in the host cell. Changes in thermodynamic and kinetic parameters lead to changes in biological parameters of infectivity and pathogenicity. SARS-CoV-2 has starting from in 2019, until today, evolved towards increase in infectivity and maintaining constant pathogenicity, or for some variants a slight decrease in pathogenicity. In the case of Omicron BQ.1, BQ.1.1, XBB and XBB.1 variants pathogenicity is identical as in the Omicron BA.2.75 variant. On the other hand, infectivity of the Omicron BQ.1, BQ.1.1, XBB and XBB.1 variants is greater than those of previous variants. This will most likely result in the phenomenon of asymmetric coinfection, that is circulation of several variants in the population, some being dominant.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

Introduction: SARS-CoV-2 infection was first reported in 2019 and has since spread throughout the world. This is a cross-sectional study in cooperation with 118 Department of Pre-Hospital and Territorial Emergency (118 SET) of Taranto City and the University of Bari, Aldo Moro, and the School of Medicine from Italy. We conducted a study on how the COVID-19 epidemics evolved and how it was contained by different countermeasures by taking into account data showing socio-demographic and that older persons, as well as individuals with comorbidities and poor metabolic health, and people coming from economically depressed areas with lower quality of life in general, are more likely to develop severe COVID-19 infection. Objective: Examine the association between county-level socio-demographic risk factors and COVID-19 incidence and mortality, determining the possible emo-biological markers, ferritin, and lymphocytes, that could be indicative of SARS-CoV-2 infection. Methods: Descriptive cross-sectional study on 600 patients examined and treated at general hospital Ninh Thuan from January to September 2022. Results: 33/600 patients were confirmed to be infected with SARS-CoV-2 (5.5%), males 4.8% and females 5.8%, the median age of infected patients is 36 years. Most infections were mild (75.8%). Our results revealed that the structure and the spatial arrangement of socio-demographic arrangements are important either as epidemiological determinants or as disease markers. Conclusion: Approximately 5.5% of patients infected with SARS-CoV-2 come to examination and treatment at the hospital, these findings suggested that possible infection rate in the burden of the COVID-19 pandemic, the sociodemographic risk factors, and their root causes must be addressed. In addition, lab results obtained from affected patients showed that lymphocytes and ferritin could be considered traits of mild COVID-19 infection.

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

Background: During the COVID-19 pandemic, hygiene behaviors such as keeping distance, avoid-ing masses, wearing face masks and adhering to hand hygiene recommendations became impera-tive. The current study aims to determine factors interrelating with hygiene behaviors. Methods: 4,049 individuals (1,305 male, 2,709 female, aged 18-80 years) were recruited from rehabilitation clinics or freely on the internet and surveyed via online questionnaire between May 2020 and August 2021. Socio-demographics, hygiene behaviors, emotions (fear), life-satisfaction, risk factors and disability as well as communication were assessed. Results: Prevalence for hygiene behaviors was: keeping the distance 84.9%, avoiding mass gatherings 84.6%, wearing face masks 96.5% and hand hygiene 80.7%. Hygiene behaviors were significantly related to fear with linear and quad-ratic associations. Conclusion: Individuals with disabilities, risk factors and psychological symp-toms are more compliant. Especially hand hygiene should be targeted to achieve higher compli-ance rates. A medium level of fear is more functional than too elevated fear. Behavioral interven-tions and targeted communication aiming at improving different behaviors in orchestration can help individuals to remain healthy and maintain a high life-satisfaction. Thereby, communication in the healthcare setting is imperative and all involved individuals should become more aware of this to ensure high hygiene standards and patient safety.

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. As of February 21, total 75,773 confirmed cases worldwide have spread to more than two dozen countries. Transmission of COVID-19 can occur early in the course of infection since SARS-CoV-2 viral loads in asymptomatic patients are similar to that in the symptomatic patients. Therefore, more sensitive diagnostic methods are needed to detect early phase of the infection to prevent secondary or tertiary spreads. Here, we compare the RT-PCR confirmatory test results using two different SARS-CoV-2 viral RNAs from two Korean COVID-19 confirmed cases.RT-PCR method targeting the RdRP gene, which was recommended by WHO guideline, was less sensitive than targeting N genes (as per CDC guideline). Because many countries follow the WHO guideline, our findings may contribute to the early diagnosis of COVID-19.

This prospective study provides data on long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison to two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. Concentration of antibodies against SARS-CoV-2 spike protein in plasma 5-7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after first vaccine dose was 86% after ChAd compared to 35% and 39% after BNT and m1273, respectively (p &lt; 0.0001), and after second vaccine dose highest (89%) in the m1273/m1273 group (p &lt; 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.